People of South Asian ancestry are more likely to develop type 2 diabetes mellitus (T2DM) at a younger age and lower BMI than people of European ancestry. The reasons for this fact are poorly understood, as the majority of genetic research on T2DM has been performed in white European populations. Now, a study in Nature Medicine has used partitioned polygenic risk scores (pPS) to uncover the genetic pathways that predispose people of British Pakistani and British Bangladeshi origin to T2DM and gestational diabetes mellitus (GDM).

The researchers next assessed whether pPS could be used to predict the responses of patients of South Asian heritage to antidiabetic medication. They found that higher pPS scores for lipodystrophy and β-cell insulin dysfunction was associated with a reduced response to metformin and sodium–glucose co-transporter 2 inhibitors and an increased likelihood of progressing to insulin treatment. Finally, the study identified that individuals with ‘extreme’ (top decile) pPS signatures for insulin deficiency and lipodystrophy had a higher risk of developing T2DM than the overall study population, were diagnosed with T2DM 8 years earlier than those with low pPS in those categories and were more likely to develop complications such as diabetic retinopathy.

与欧洲血统的人相比，南亚血统的人更有可能在更年轻时患上 2 型糖尿病 （T2DM），并且 BMI 更低。这一事实的原因知之甚少，因为大多数关于 T2DM 的遗传研究都是在欧洲白人人群中进行的。现在，《自然医学》上的一项研究使用分区多基因风险评分 （pPS） 来揭示使英属巴基斯坦人和英属孟加拉国裔人易患 T2DM 和妊娠糖尿病 （GDM） 的遗传途径。

研究人员接下来评估了 pPS 是否可用于预测南亚裔患者对抗糖尿病药物的反应。他们发现，脂肪代谢障碍和β细胞胰岛素功能障碍的 pPS 评分较高与对二甲双胍和钠-葡萄糖协同转运蛋白 2 抑制剂的反应降低以及进展为胰岛素治疗的可能性增加有关。最后，该研究发现，与整个研究人群相比，具有胰岛素缺乏和脂肪代谢障碍的“极端”（最高十分位数）pPS 特征的个体患 T2DM 的风险更高，被诊断出患有 T2DM 的时间比这些类别中 pPS 低的人早 8 年，并且更有可能发生并发症，例如糖尿病视网膜病变。